Abstract
Following discovery that the type of kidney neoplasm induced in protein-deprived Wistar rats by a single dose of dimethylnitrosamine (DMN) was age-dependent, this study aimed to refine the system in order to develop a high frequency model for the induction of cortical epithelial tumors with low mesenchymal tumor incidence. Using outbred female Crl:(W)BR (Charles River Wistar) rats, DMN at a dose of 30 mg/kg was administered at 9-10 weeks of age following a 5-day period of high-carbohydrate/no-protein diet. From a total of 49 rats, 43 survived the early toxicity and 91% of these developed renal tumors. Mesenchymal tumors were present in only 9% of the tumor-bearing animals. In contrast, 70% of the rats developed epithelial tumors of the tubules classifiable on a size and histological basis as adenocarcinomas/carcinomas in response to DMN. A further 21% of rats had smaller proliferative lesions designated as adenomas, making the total cortical epithelial tumor incidence in excess of 90%. The malignant potential of the epithelial tumors was underscored by the presence of metastatic invasion, mainly involving the lungs, in 15% of the tumor-bearing rats. Metastatic behavior correlated with progressive growth of the carcinomas over a period of time exceeding 1.5 years to dimensions usually exceeding 2.9 cm diameter. Of the tumors approaching or exceeding this size, the metastatic rate was almost 50%. Thus, the administration of DMN to 65-70 days old, protein-deprived Wistar rats provides a potent, single dose model for the study of renal epithelial carcinogenesis with insignificant mesenchymal tumor induction and without the continuing toxicity which perturbs regimens based on repeated or continuous exposures.
Published Version
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